An understanding of unique properties of stem and progenitor cells is advancing rapidly. Initial successes in manipulating such cells for therapeutic advantages have intensified investigations (and enabled national centers that focus on embryonic stem cell plasticity, adult stem cell sources &potentials, and therapies for defined disorders). This revolution has opened new doors, but has also raised important new questions concerning key niche-specific regulators of progenitor cell growth, survival, and development. Our COBRE Program has been developed to address such questions. In Phase-l, we have: assembled a thematically focused team of talented investigators;engaged expert IAC, EAC and mentoring components;acquired several R01 and K01 awards;made major infrastructural advances (e.g., new cores in cell separation, histopathology, bioinformatics and a new research building addition);and have extended intra-inter Institute interactions. Impacting scientific discoveries also have been made. In Phase-ll, aims are to: #1 Support six exciting new research projects to advance mechanistic understanding of blood, vascular, neural, and skeletal muscle progenitor cell development in important disease and injury contexts;#2 Guide additional investigators to R01 funded status, recruit an additional senior scientist and at least two additional outstanding new junior investigators to bolster our Program;#3 Further develop key core facilities;#4 Continue to fortify infrastructure (new research wing, State biomedical bonds);and #5 Support new interactive seed projects towards synergistic co-investigator programs, and grant support. We will continue to investigate important niche-specific progenitor cell problems, and will focus on: BMP orthologue regulation of kidney response to injury and regeneration;R-spondin2 as a novel candidate regulator of skeletal muscle regeneration;Mechanisms of mural cell assisted de novo blood vessel formation from hES cells;DNA break repair in stem cells and affected microenvironments during lymphomagenesis;Slug as a key regulator of hematopoietic stem cell survival;and Jagged 1 maintenance of neural stem cell expansion and pluripotency. These projects share common scientific (and clinically relevant) themes;will foster state and national interactions;will advance the field (and funding) in significant ways;and will attract additional high caliber investigators to our Program. Overall efforts will forge a nationally competitive Center in this exciting discipline.